Neurology Reviews

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Morton J, MD, a 68-year-old cardiologist based in the Midwest, saw things become dramatically worse when his nine-physician practice was taken over by a large health system.

“Everything changed. My partners and I lost a lot of autonomy. We had a say – but not the final say-so in who we hired as medical assistants or receptionists. We had to change how long we spent with patients and justify procedures or tests – not just to the insurance companies, which is an old story, but to our new employer,” said Dr. J, who asked to remain anonymous.

Worst of all, “I had to report to a kid – a doctor in his 30s, someone young enough to be my son, someone with a fraction of the clinical training and experience I had but who now got to tell me what to do and how to run my practice.”

The “final straw” for Dr. J came when the practice had to change to a new electronic health record (EHR) system. “Learning this new system was like pulling teeth,” he said. His youthful supervisor was “obviously impatient and irritated – his whole attitude and demeanor reflected a sense that he was saddled with a dinosaur.”

After much anguishing and soul-searching, Dr. J decided to retire. “I was already close to retirement age, and I thought it would be nice to spend more time with my grandchildren. Feeling so disrespected was simply the catalyst that brought the decision to a head a couple of years sooner than I had planned.”
 

Getting through a delicate discussion

This unfortunate situation could have been avoided had the younger supervisor shown more sensitivity, says otolaryngologist Mark Wallace, DO.

Dr. Wallace is speaking from personal experience. Early in his career, he was a younger physician who was forced to discuss a practice management issue with an older physician.

Dr. Wallace was a member of a committee that was responsible for “maximizing the efficiency of good care, while still being aware of cost issues.” When the committee “wanted one of the physicians in the group to change their behavior to improve cost savings, it was my job to discuss that with them.”

Dr. Wallace, who today is a locum tenens physician and a medical practice consultant to Physicians Thrive – an advisory group that helps physicians with financial and practice management problems – recalls feeling uncomfortable about broaching the subject to his supervisee. In this case, the older physician was prescribing name brand medications, and the committee that appointed Dr. Wallace wanted him to encourage the physician to prescribe a generic medication first and reserve brand prescriptions only for cases in which the generic was ineffective.

He acknowledges that he thought the generic was equivalent to the branded product in safety and efficacy.

“I always felt this to be a delicate discussion, whatever the age of the physician, because I didn’t like the idea of telling a doctor that they have to change how they practice so as to save money. I would never want anyone to feel they’re providing a lower level of care.”

The fact that this was an older physician – in his 60s – compounded his hesitancy. “Older physicians have a lot more experience than what I had in my 30s,” Dr. Wallace said. “I could talk to them about studies and outcomes and things like that, but a large part of medicine is the experience you gain over time.

“I presented it simply as a cost issue raised by the committee and asked him to consider experimenting with changing his prescribing behavior, while emphasizing that ultimately, it was his decision,” says Dr. Wallace.

The supervisee understood the concern and agreed to the experiment. He ended up prescribing the generic more frequently, although perhaps not as frequently as the committee would have liked.

Respectful, authentic, honest communication is important in any leadership situation but especially in those in which younger physicians are supervising physicians who are old enough to be their parents, says Ted Epperly, MD, a family physician in Boise, Idaho, and president and CEO of Family Medicine Residency of Idaho.

Dr. Wallace said that older physicians, on coming out of training, felt more respected, were better paid, and didn’t have to continually adjust to new regulations and new complicated insurance requirements. Today’s young physicians coming out of training may not find the practice of medicine as enjoyable as their older counterparts did, but they are accustomed to increasingly complex rules and regulations, so it’s less of an adjustment. But many may not feel they want to work 80 hours per week, as their older counterparts did.
 

Challenges of technology

Technology is one of the most central areas where intergenerational differences play out, says Tracy Clarke, chief human resources officer at Kitsap Mental Health Services, a large nonprofit organization in Bremerton, Wash., that employs roughly 500 individuals. “The younger physicians in our practice are really prepared, already engaged in technology, and used to using technology for documentation, and it is already integrated into the way they do business in general and practice,” she said.

Dr. Epperly noted that Gen X-ers are typically comfortable with digital technology, although not quite as much as the following generation, the millennials, who have grown up with smartphones and computers quite literally at their fingertips from earliest childhood.

Dr. Epperly, now 67, described the experience of having his organization convert to a new EHR system. “Although the younger physicians were not my supervisors, the dynamic that occurred when we were switching to the new system is typical of what might happen in a more formal reporting structure of older ‘supervisee’ and younger supervisor,” he said. In fact, his experience was similar to that of Dr. J.

“Some of the millennials were so quick to learn the new system that they forgot to check in with the older ones about how they were doing, or they were frustrated with our slow pace of learning the new technology,” said Dr. Epperly. “In fact, I was struggling to master it, and so were many others of my generation, and I felt very dumb, slow, and vulnerable, even though I usually regard myself as a pretty bright guy.”

Dr. Epperly encourages younger physicians not to think, “He’s asked me five times how to do this – what’s his problem?” This impatience can be intuited by the older physician, who may take it personally and feel devalued and disrespected.

Joy Engblade, an internal medicine physician and CMO of Northern Inyo Hospital, Bishop, Calif., said that when her institution was transitioning to a new EHR system this past May, she was worried that the older physicians would have the most difficulty.

Ironically, that turned out not to be the case. In fact, the younger physicians struggled more because the older physicians recognized their limitations and “were willing to do whatever we asked them to do. They watched the tutorials about how to use the new EHR. They went to every class that was offered and did all the practice sessions.” By contrast, many of the younger ones thought, “I know how to work an EHR, I’ve been doing it for years, so how hard could it be?” By the time they needed to actually use it, the instructional resources and tutorials were no longer available.

Dr. Epperly’s experience is different. He noted that some older physicians may be embarrassed to acknowledge that they are technologically challenged and may say, “I got it, I understand,” when they are still struggling to master the new technology.

Ms. Clarke notes that the leadership in her organization is younger than many of the physicians who report to them. “For the leadership, the biggest challenge is that many older physicians are set in their ways, and they haven’t really seen a reason to change their practice or ways of doing things.” For example, some still prefer paper charting or making voice recordings of patient visits for other people to transcribe.

Ms. Clarke has some advice for younger leaders: “Really explore what the pain points are of these older physicians. Beyond their saying, ‘because I’ve always done it this way,’ what really is the advantage of, for example, paper charting when using the EHR is more efficient?”

Daniel DeBehnke, MD, is an emergency medicine physician and vice president and chief physician executive for Premier Inc., where he helps hospitals improve quality, safety, and financial performance. Before joining Premier, he was both a practicing physician and CEO of a health system consisting of more than 1,500 physicians.

“Having been on both sides of the spectrum as manager/leader within a physician group, some of whom are senior to me and some of whom are junior, I can tell you that I have never had any issues related to the age gap.” In fact, it is less about age per se and more about “the expertise that you, as a manager, bring to the table in understanding the nuances of the medical practice and for the individual being ‘managed.’ It is about trusting the expertise of the manager.”
 

Before and after hourly caps

Dr. Engblade regards “generational” issues to be less about age and birth year and more about the cap on hours worked during residency.

Dr. Engblade, who is 45 years old, said she did her internship year with no hourly restrictions. Such restrictions only went into effect during her second year of residency. “This created a paradigm shift in how much people wanted to work and created a consciousness of work-life balance that hadn’t been part of the conversation before,” she said.

When she interviews an older physician, a typical response is, “Of course I’ll be available any time,” whereas younger physicians, who went through residency after hourly restrictions had been established, are more likely to ask how many hours they will be on and how many they’ll be off.

Matt Lambert, MD, an independent emergency medicine physician and CMO of Curation Health, Washington, agreed, noting that differences in the cap on hours during training “can create a bit of an undertow, a tension between younger managers who are better adjusted in terms of work-life balance and older physicians being managed, who have a different work ethic and also might regard their managers as being less trained because they put in fewer hours during training.”

It is also important to be cognizant of differences in style and priorities that each generation brings to the table. Jaciel Keltgen, PhD, assistant professor of business administration, Augustana University, Sioux Falls, S.D., has heard older physicians say, “We did this the hard way, we sacrificed for our organization, and we expect the same values of younger physicians.” The younger ones tend to say, “We need to use all the tools at our disposal, and medicine doesn’t have to be practiced the way it’s always been.”

Dr. Keltgen, whose PhD is in political science and who has studied public administration, said that younger physicians may also question the mores and protocols that older physicians take for granted. For example, when her physician son was beginning his career, he was told by his senior supervisors that although he was “performing beautifully as a physician, he needed to shave more frequently, wear his white coat more often, and introduce himself as ‘Doctor’ rather than by his first name. Although he did wear his white coat more often, he didn’t change how he introduced himself to patients.”

Flexibility and mutual understanding of each generation’s needs, the type, structure, and amount of training they underwent, and the prevailing values will smooth supervisory interactions and optimize outcomes, experts agree.
 

Every generation’s No. 1 concern

For her dissertation, Dr. Keltgen used a large dataset of physicians and sought to draw a predictive model by generation and gender as to what physicians were seeking in order to be satisfied in their careers. One “overwhelming finding” of her research into generational differences in physicians is that “every single generation and gender is there to promote the health of their patients, and providing excellent care is their No. 1 concern. That is the common focus and the foundation that everyone can build on.”

Dr. J agreed. “Had I felt like a valued collaborator, I might have made a different decision.” He has begun to consider reentering clinical practice, perhaps as locum tenens or on a part-time basis. “I don’t want to feel that I’ve been driven out of a field that I love. I will see if I can find some type of context where my experience will be valued and learn to bring myself up to speed with technology if necessary. I believe I still have much to offer patients, and I would like to find a context to do so.”

A version of this article first appeared on Medscape.com.

Morton J, MD, a 68-year-old cardiologist based in the Midwest, saw things become dramatically worse when his nine-physician practice was taken over by a large health system.

“Everything changed. My partners and I lost a lot of autonomy. We had a say – but not the final say-so in who we hired as medical assistants or receptionists. We had to change how long we spent with patients and justify procedures or tests – not just to the insurance companies, which is an old story, but to our new employer,” said Dr. J, who asked to remain anonymous.

Worst of all, “I had to report to a kid – a doctor in his 30s, someone young enough to be my son, someone with a fraction of the clinical training and experience I had but who now got to tell me what to do and how to run my practice.”

The “final straw” for Dr. J came when the practice had to change to a new electronic health record (EHR) system. “Learning this new system was like pulling teeth,” he said. His youthful supervisor was “obviously impatient and irritated – his whole attitude and demeanor reflected a sense that he was saddled with a dinosaur.”

After much anguishing and soul-searching, Dr. J decided to retire. “I was already close to retirement age, and I thought it would be nice to spend more time with my grandchildren. Feeling so disrespected was simply the catalyst that brought the decision to a head a couple of years sooner than I had planned.”
 

Getting through a delicate discussion

This unfortunate situation could have been avoided had the younger supervisor shown more sensitivity, says otolaryngologist Mark Wallace, DO.

Dr. Wallace is speaking from personal experience. Early in his career, he was a younger physician who was forced to discuss a practice management issue with an older physician.

Dr. Wallace was a member of a committee that was responsible for “maximizing the efficiency of good care, while still being aware of cost issues.” When the committee “wanted one of the physicians in the group to change their behavior to improve cost savings, it was my job to discuss that with them.”

Dr. Wallace, who today is a locum tenens physician and a medical practice consultant to Physicians Thrive – an advisory group that helps physicians with financial and practice management problems – recalls feeling uncomfortable about broaching the subject to his supervisee. In this case, the older physician was prescribing name brand medications, and the committee that appointed Dr. Wallace wanted him to encourage the physician to prescribe a generic medication first and reserve brand prescriptions only for cases in which the generic was ineffective.

He acknowledges that he thought the generic was equivalent to the branded product in safety and efficacy.

“I always felt this to be a delicate discussion, whatever the age of the physician, because I didn’t like the idea of telling a doctor that they have to change how they practice so as to save money. I would never want anyone to feel they’re providing a lower level of care.”

The fact that this was an older physician – in his 60s – compounded his hesitancy. “Older physicians have a lot more experience than what I had in my 30s,” Dr. Wallace said. “I could talk to them about studies and outcomes and things like that, but a large part of medicine is the experience you gain over time.

“I presented it simply as a cost issue raised by the committee and asked him to consider experimenting with changing his prescribing behavior, while emphasizing that ultimately, it was his decision,” says Dr. Wallace.

The supervisee understood the concern and agreed to the experiment. He ended up prescribing the generic more frequently, although perhaps not as frequently as the committee would have liked.

Respectful, authentic, honest communication is important in any leadership situation but especially in those in which younger physicians are supervising physicians who are old enough to be their parents, says Ted Epperly, MD, a family physician in Boise, Idaho, and president and CEO of Family Medicine Residency of Idaho.

Dr. Wallace said that older physicians, on coming out of training, felt more respected, were better paid, and didn’t have to continually adjust to new regulations and new complicated insurance requirements. Today’s young physicians coming out of training may not find the practice of medicine as enjoyable as their older counterparts did, but they are accustomed to increasingly complex rules and regulations, so it’s less of an adjustment. But many may not feel they want to work 80 hours per week, as their older counterparts did.
 

Challenges of technology

Technology is one of the most central areas where intergenerational differences play out, says Tracy Clarke, chief human resources officer at Kitsap Mental Health Services, a large nonprofit organization in Bremerton, Wash., that employs roughly 500 individuals. “The younger physicians in our practice are really prepared, already engaged in technology, and used to using technology for documentation, and it is already integrated into the way they do business in general and practice,” she said.

Dr. Epperly noted that Gen X-ers are typically comfortable with digital technology, although not quite as much as the following generation, the millennials, who have grown up with smartphones and computers quite literally at their fingertips from earliest childhood.

Dr. Epperly, now 67, described the experience of having his organization convert to a new EHR system. “Although the younger physicians were not my supervisors, the dynamic that occurred when we were switching to the new system is typical of what might happen in a more formal reporting structure of older ‘supervisee’ and younger supervisor,” he said. In fact, his experience was similar to that of Dr. J.

“Some of the millennials were so quick to learn the new system that they forgot to check in with the older ones about how they were doing, or they were frustrated with our slow pace of learning the new technology,” said Dr. Epperly. “In fact, I was struggling to master it, and so were many others of my generation, and I felt very dumb, slow, and vulnerable, even though I usually regard myself as a pretty bright guy.”

Dr. Epperly encourages younger physicians not to think, “He’s asked me five times how to do this – what’s his problem?” This impatience can be intuited by the older physician, who may take it personally and feel devalued and disrespected.

Joy Engblade, an internal medicine physician and CMO of Northern Inyo Hospital, Bishop, Calif., said that when her institution was transitioning to a new EHR system this past May, she was worried that the older physicians would have the most difficulty.

Ironically, that turned out not to be the case. In fact, the younger physicians struggled more because the older physicians recognized their limitations and “were willing to do whatever we asked them to do. They watched the tutorials about how to use the new EHR. They went to every class that was offered and did all the practice sessions.” By contrast, many of the younger ones thought, “I know how to work an EHR, I’ve been doing it for years, so how hard could it be?” By the time they needed to actually use it, the instructional resources and tutorials were no longer available.

Dr. Epperly’s experience is different. He noted that some older physicians may be embarrassed to acknowledge that they are technologically challenged and may say, “I got it, I understand,” when they are still struggling to master the new technology.

Ms. Clarke notes that the leadership in her organization is younger than many of the physicians who report to them. “For the leadership, the biggest challenge is that many older physicians are set in their ways, and they haven’t really seen a reason to change their practice or ways of doing things.” For example, some still prefer paper charting or making voice recordings of patient visits for other people to transcribe.

Ms. Clarke has some advice for younger leaders: “Really explore what the pain points are of these older physicians. Beyond their saying, ‘because I’ve always done it this way,’ what really is the advantage of, for example, paper charting when using the EHR is more efficient?”

Daniel DeBehnke, MD, is an emergency medicine physician and vice president and chief physician executive for Premier Inc., where he helps hospitals improve quality, safety, and financial performance. Before joining Premier, he was both a practicing physician and CEO of a health system consisting of more than 1,500 physicians.

“Having been on both sides of the spectrum as manager/leader within a physician group, some of whom are senior to me and some of whom are junior, I can tell you that I have never had any issues related to the age gap.” In fact, it is less about age per se and more about “the expertise that you, as a manager, bring to the table in understanding the nuances of the medical practice and for the individual being ‘managed.’ It is about trusting the expertise of the manager.”
 

Before and after hourly caps

Dr. Engblade regards “generational” issues to be less about age and birth year and more about the cap on hours worked during residency.

Dr. Engblade, who is 45 years old, said she did her internship year with no hourly restrictions. Such restrictions only went into effect during her second year of residency. “This created a paradigm shift in how much people wanted to work and created a consciousness of work-life balance that hadn’t been part of the conversation before,” she said.

When she interviews an older physician, a typical response is, “Of course I’ll be available any time,” whereas younger physicians, who went through residency after hourly restrictions had been established, are more likely to ask how many hours they will be on and how many they’ll be off.

Matt Lambert, MD, an independent emergency medicine physician and CMO of Curation Health, Washington, agreed, noting that differences in the cap on hours during training “can create a bit of an undertow, a tension between younger managers who are better adjusted in terms of work-life balance and older physicians being managed, who have a different work ethic and also might regard their managers as being less trained because they put in fewer hours during training.”

It is also important to be cognizant of differences in style and priorities that each generation brings to the table. Jaciel Keltgen, PhD, assistant professor of business administration, Augustana University, Sioux Falls, S.D., has heard older physicians say, “We did this the hard way, we sacrificed for our organization, and we expect the same values of younger physicians.” The younger ones tend to say, “We need to use all the tools at our disposal, and medicine doesn’t have to be practiced the way it’s always been.”

Dr. Keltgen, whose PhD is in political science and who has studied public administration, said that younger physicians may also question the mores and protocols that older physicians take for granted. For example, when her physician son was beginning his career, he was told by his senior supervisors that although he was “performing beautifully as a physician, he needed to shave more frequently, wear his white coat more often, and introduce himself as ‘Doctor’ rather than by his first name. Although he did wear his white coat more often, he didn’t change how he introduced himself to patients.”

Flexibility and mutual understanding of each generation’s needs, the type, structure, and amount of training they underwent, and the prevailing values will smooth supervisory interactions and optimize outcomes, experts agree.
 

Every generation’s No. 1 concern

For her dissertation, Dr. Keltgen used a large dataset of physicians and sought to draw a predictive model by generation and gender as to what physicians were seeking in order to be satisfied in their careers. One “overwhelming finding” of her research into generational differences in physicians is that “every single generation and gender is there to promote the health of their patients, and providing excellent care is their No. 1 concern. That is the common focus and the foundation that everyone can build on.”

Dr. J agreed. “Had I felt like a valued collaborator, I might have made a different decision.” He has begun to consider reentering clinical practice, perhaps as locum tenens or on a part-time basis. “I don’t want to feel that I’ve been driven out of a field that I love. I will see if I can find some type of context where my experience will be valued and learn to bring myself up to speed with technology if necessary. I believe I still have much to offer patients, and I would like to find a context to do so.”

A version of this article first appeared on Medscape.com.

Morton J, MD, a 68-year-old cardiologist based in the Midwest, saw things become dramatically worse when his nine-physician practice was taken over by a large health system.

“Everything changed. My partners and I lost a lot of autonomy. We had a say – but not the final say-so in who we hired as medical assistants or receptionists. We had to change how long we spent with patients and justify procedures or tests – not just to the insurance companies, which is an old story, but to our new employer,” said Dr. J, who asked to remain anonymous.

Worst of all, “I had to report to a kid – a doctor in his 30s, someone young enough to be my son, someone with a fraction of the clinical training and experience I had but who now got to tell me what to do and how to run my practice.”

The “final straw” for Dr. J came when the practice had to change to a new electronic health record (EHR) system. “Learning this new system was like pulling teeth,” he said. His youthful supervisor was “obviously impatient and irritated – his whole attitude and demeanor reflected a sense that he was saddled with a dinosaur.”

After much anguishing and soul-searching, Dr. J decided to retire. “I was already close to retirement age, and I thought it would be nice to spend more time with my grandchildren. Feeling so disrespected was simply the catalyst that brought the decision to a head a couple of years sooner than I had planned.”
 

Getting through a delicate discussion

This unfortunate situation could have been avoided had the younger supervisor shown more sensitivity, says otolaryngologist Mark Wallace, DO.

Dr. Wallace is speaking from personal experience. Early in his career, he was a younger physician who was forced to discuss a practice management issue with an older physician.

Dr. Wallace was a member of a committee that was responsible for “maximizing the efficiency of good care, while still being aware of cost issues.” When the committee “wanted one of the physicians in the group to change their behavior to improve cost savings, it was my job to discuss that with them.”

Dr. Wallace, who today is a locum tenens physician and a medical practice consultant to Physicians Thrive – an advisory group that helps physicians with financial and practice management problems – recalls feeling uncomfortable about broaching the subject to his supervisee. In this case, the older physician was prescribing name brand medications, and the committee that appointed Dr. Wallace wanted him to encourage the physician to prescribe a generic medication first and reserve brand prescriptions only for cases in which the generic was ineffective.

He acknowledges that he thought the generic was equivalent to the branded product in safety and efficacy.

“I always felt this to be a delicate discussion, whatever the age of the physician, because I didn’t like the idea of telling a doctor that they have to change how they practice so as to save money. I would never want anyone to feel they’re providing a lower level of care.”

The fact that this was an older physician – in his 60s – compounded his hesitancy. “Older physicians have a lot more experience than what I had in my 30s,” Dr. Wallace said. “I could talk to them about studies and outcomes and things like that, but a large part of medicine is the experience you gain over time.

“I presented it simply as a cost issue raised by the committee and asked him to consider experimenting with changing his prescribing behavior, while emphasizing that ultimately, it was his decision,” says Dr. Wallace.

The supervisee understood the concern and agreed to the experiment. He ended up prescribing the generic more frequently, although perhaps not as frequently as the committee would have liked.

Respectful, authentic, honest communication is important in any leadership situation but especially in those in which younger physicians are supervising physicians who are old enough to be their parents, says Ted Epperly, MD, a family physician in Boise, Idaho, and president and CEO of Family Medicine Residency of Idaho.

Dr. Wallace said that older physicians, on coming out of training, felt more respected, were better paid, and didn’t have to continually adjust to new regulations and new complicated insurance requirements. Today’s young physicians coming out of training may not find the practice of medicine as enjoyable as their older counterparts did, but they are accustomed to increasingly complex rules and regulations, so it’s less of an adjustment. But many may not feel they want to work 80 hours per week, as their older counterparts did.
 

Challenges of technology

Technology is one of the most central areas where intergenerational differences play out, says Tracy Clarke, chief human resources officer at Kitsap Mental Health Services, a large nonprofit organization in Bremerton, Wash., that employs roughly 500 individuals. “The younger physicians in our practice are really prepared, already engaged in technology, and used to using technology for documentation, and it is already integrated into the way they do business in general and practice,” she said.

Dr. Epperly noted that Gen X-ers are typically comfortable with digital technology, although not quite as much as the following generation, the millennials, who have grown up with smartphones and computers quite literally at their fingertips from earliest childhood.

Dr. Epperly, now 67, described the experience of having his organization convert to a new EHR system. “Although the younger physicians were not my supervisors, the dynamic that occurred when we were switching to the new system is typical of what might happen in a more formal reporting structure of older ‘supervisee’ and younger supervisor,” he said. In fact, his experience was similar to that of Dr. J.

“Some of the millennials were so quick to learn the new system that they forgot to check in with the older ones about how they were doing, or they were frustrated with our slow pace of learning the new technology,” said Dr. Epperly. “In fact, I was struggling to master it, and so were many others of my generation, and I felt very dumb, slow, and vulnerable, even though I usually regard myself as a pretty bright guy.”

Dr. Epperly encourages younger physicians not to think, “He’s asked me five times how to do this – what’s his problem?” This impatience can be intuited by the older physician, who may take it personally and feel devalued and disrespected.

Joy Engblade, an internal medicine physician and CMO of Northern Inyo Hospital, Bishop, Calif., said that when her institution was transitioning to a new EHR system this past May, she was worried that the older physicians would have the most difficulty.

Ironically, that turned out not to be the case. In fact, the younger physicians struggled more because the older physicians recognized their limitations and “were willing to do whatever we asked them to do. They watched the tutorials about how to use the new EHR. They went to every class that was offered and did all the practice sessions.” By contrast, many of the younger ones thought, “I know how to work an EHR, I’ve been doing it for years, so how hard could it be?” By the time they needed to actually use it, the instructional resources and tutorials were no longer available.

Dr. Epperly’s experience is different. He noted that some older physicians may be embarrassed to acknowledge that they are technologically challenged and may say, “I got it, I understand,” when they are still struggling to master the new technology.

Ms. Clarke notes that the leadership in her organization is younger than many of the physicians who report to them. “For the leadership, the biggest challenge is that many older physicians are set in their ways, and they haven’t really seen a reason to change their practice or ways of doing things.” For example, some still prefer paper charting or making voice recordings of patient visits for other people to transcribe.

Ms. Clarke has some advice for younger leaders: “Really explore what the pain points are of these older physicians. Beyond their saying, ‘because I’ve always done it this way,’ what really is the advantage of, for example, paper charting when using the EHR is more efficient?”

Daniel DeBehnke, MD, is an emergency medicine physician and vice president and chief physician executive for Premier Inc., where he helps hospitals improve quality, safety, and financial performance. Before joining Premier, he was both a practicing physician and CEO of a health system consisting of more than 1,500 physicians.

“Having been on both sides of the spectrum as manager/leader within a physician group, some of whom are senior to me and some of whom are junior, I can tell you that I have never had any issues related to the age gap.” In fact, it is less about age per se and more about “the expertise that you, as a manager, bring to the table in understanding the nuances of the medical practice and for the individual being ‘managed.’ It is about trusting the expertise of the manager.”
 

Before and after hourly caps

Dr. Engblade regards “generational” issues to be less about age and birth year and more about the cap on hours worked during residency.

Dr. Engblade, who is 45 years old, said she did her internship year with no hourly restrictions. Such restrictions only went into effect during her second year of residency. “This created a paradigm shift in how much people wanted to work and created a consciousness of work-life balance that hadn’t been part of the conversation before,” she said.

When she interviews an older physician, a typical response is, “Of course I’ll be available any time,” whereas younger physicians, who went through residency after hourly restrictions had been established, are more likely to ask how many hours they will be on and how many they’ll be off.

Matt Lambert, MD, an independent emergency medicine physician and CMO of Curation Health, Washington, agreed, noting that differences in the cap on hours during training “can create a bit of an undertow, a tension between younger managers who are better adjusted in terms of work-life balance and older physicians being managed, who have a different work ethic and also might regard their managers as being less trained because they put in fewer hours during training.”

It is also important to be cognizant of differences in style and priorities that each generation brings to the table. Jaciel Keltgen, PhD, assistant professor of business administration, Augustana University, Sioux Falls, S.D., has heard older physicians say, “We did this the hard way, we sacrificed for our organization, and we expect the same values of younger physicians.” The younger ones tend to say, “We need to use all the tools at our disposal, and medicine doesn’t have to be practiced the way it’s always been.”

Dr. Keltgen, whose PhD is in political science and who has studied public administration, said that younger physicians may also question the mores and protocols that older physicians take for granted. For example, when her physician son was beginning his career, he was told by his senior supervisors that although he was “performing beautifully as a physician, he needed to shave more frequently, wear his white coat more often, and introduce himself as ‘Doctor’ rather than by his first name. Although he did wear his white coat more often, he didn’t change how he introduced himself to patients.”

Flexibility and mutual understanding of each generation’s needs, the type, structure, and amount of training they underwent, and the prevailing values will smooth supervisory interactions and optimize outcomes, experts agree.
 

Every generation’s No. 1 concern

For her dissertation, Dr. Keltgen used a large dataset of physicians and sought to draw a predictive model by generation and gender as to what physicians were seeking in order to be satisfied in their careers. One “overwhelming finding” of her research into generational differences in physicians is that “every single generation and gender is there to promote the health of their patients, and providing excellent care is their No. 1 concern. That is the common focus and the foundation that everyone can build on.”

Dr. J agreed. “Had I felt like a valued collaborator, I might have made a different decision.” He has begun to consider reentering clinical practice, perhaps as locum tenens or on a part-time basis. “I don’t want to feel that I’ve been driven out of a field that I love. I will see if I can find some type of context where my experience will be valued and learn to bring myself up to speed with technology if necessary. I believe I still have much to offer patients, and I would like to find a context to do so.”

A version of this article first appeared on Medscape.com.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.

In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.

“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.

Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
 

Results

The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).

The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).

With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.

With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).

In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.

“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.

“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.

“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.

In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.

“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”

The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.

“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.

This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.

A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.

In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.

“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.

Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
 

Results

The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).

The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).

With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.

With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).

In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.

“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.

“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.

“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.

In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.

“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”

The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.

“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.

This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.

A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.

In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.

“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.

Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
 

Results

The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).

The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).

With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.

With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).

In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.

“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.

“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.

“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.

In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.

“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”

The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.

“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.

This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

I don’t have a patient portal. Probably never will.

This isn’t an attempt at “information blocking,” or intentional noncompliance, or a rebellious streak against the CURES act.

It’s practical: I can’t afford it.

I’m a small one-doc practice. My overhead is high, my profit margin is razor thin. In the sudden spike of COVID-19– and war-related inflation, my gas and office supply costs have gone up, but I’m in a field where I can’t raise my own prices to compensate. The restaurants and grocery stores near me can, but I can’t because of the way insurance works.

With that background, I don’t have the money to set up a patient portal for people to be able to get their notes, test results, anything.

This isn’t to say that I withhold things from patients. If they want a copy of my note, or their MRI report, or whatever, they’re welcome to it. I’m happy to fax it to them, or put it in the mail, or have them come by and pick it up.

I have no desire to keep information from patients. I actually try to stay on top of it, calling them with test results within 24 hours of receiving them and arranging follow-ups quickly when needed.

That’s one of the pluses of my dinky practice – I generally know my patients and can make decisions quickly on the next step once results come in. They don’t get tossed in a box to be reviewed in a few days. I take pride in staying on top of things – isn’t that how we all want to be treated when we’re on the other side of the desk?

Politicians like to say how much America depends on small businesses and how important we are to the economy. They love to do photo ops at a newly opened ice cream place or small barbecue joint. But if you’re a doctor in a small practice, you often get treated the same way the Mega-Med Group (“287 doctors! 19 specialties! 37 offices! No waiting!”) is treated. They can afford to have a digital portal, so why can’t you?

Just because I don’t have a patient portal, though, doesn’t mean I’m hiding things from patients.

Or not doing my best to care for them.

Like Avis, I may not be No. 1, but I sure try harder.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t have a patient portal. Probably never will.

This isn’t an attempt at “information blocking,” or intentional noncompliance, or a rebellious streak against the CURES act.

It’s practical: I can’t afford it.

I’m a small one-doc practice. My overhead is high, my profit margin is razor thin. In the sudden spike of COVID-19– and war-related inflation, my gas and office supply costs have gone up, but I’m in a field where I can’t raise my own prices to compensate. The restaurants and grocery stores near me can, but I can’t because of the way insurance works.

With that background, I don’t have the money to set up a patient portal for people to be able to get their notes, test results, anything.

This isn’t to say that I withhold things from patients. If they want a copy of my note, or their MRI report, or whatever, they’re welcome to it. I’m happy to fax it to them, or put it in the mail, or have them come by and pick it up.

I have no desire to keep information from patients. I actually try to stay on top of it, calling them with test results within 24 hours of receiving them and arranging follow-ups quickly when needed.

That’s one of the pluses of my dinky practice – I generally know my patients and can make decisions quickly on the next step once results come in. They don’t get tossed in a box to be reviewed in a few days. I take pride in staying on top of things – isn’t that how we all want to be treated when we’re on the other side of the desk?

Politicians like to say how much America depends on small businesses and how important we are to the economy. They love to do photo ops at a newly opened ice cream place or small barbecue joint. But if you’re a doctor in a small practice, you often get treated the same way the Mega-Med Group (“287 doctors! 19 specialties! 37 offices! No waiting!”) is treated. They can afford to have a digital portal, so why can’t you?

Just because I don’t have a patient portal, though, doesn’t mean I’m hiding things from patients.

Or not doing my best to care for them.

Like Avis, I may not be No. 1, but I sure try harder.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t have a patient portal. Probably never will.

This isn’t an attempt at “information blocking,” or intentional noncompliance, or a rebellious streak against the CURES act.

It’s practical: I can’t afford it.

I’m a small one-doc practice. My overhead is high, my profit margin is razor thin. In the sudden spike of COVID-19– and war-related inflation, my gas and office supply costs have gone up, but I’m in a field where I can’t raise my own prices to compensate. The restaurants and grocery stores near me can, but I can’t because of the way insurance works.

With that background, I don’t have the money to set up a patient portal for people to be able to get their notes, test results, anything.

This isn’t to say that I withhold things from patients. If they want a copy of my note, or their MRI report, or whatever, they’re welcome to it. I’m happy to fax it to them, or put it in the mail, or have them come by and pick it up.

I have no desire to keep information from patients. I actually try to stay on top of it, calling them with test results within 24 hours of receiving them and arranging follow-ups quickly when needed.

That’s one of the pluses of my dinky practice – I generally know my patients and can make decisions quickly on the next step once results come in. They don’t get tossed in a box to be reviewed in a few days. I take pride in staying on top of things – isn’t that how we all want to be treated when we’re on the other side of the desk?

Politicians like to say how much America depends on small businesses and how important we are to the economy. They love to do photo ops at a newly opened ice cream place or small barbecue joint. But if you’re a doctor in a small practice, you often get treated the same way the Mega-Med Group (“287 doctors! 19 specialties! 37 offices! No waiting!”) is treated. They can afford to have a digital portal, so why can’t you?

Just because I don’t have a patient portal, though, doesn’t mean I’m hiding things from patients.

Or not doing my best to care for them.

Like Avis, I may not be No. 1, but I sure try harder.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.